We followed until December 2007 a population-based cohort of Pima Indians who were invited every two years to participate in a research examinination. The methods for this longitudinal study are described in detail in Project Numbers Z01 DK069097 and Z01 DK069000. Electrocardiograms were obtained and serum total cholesterol, HDL cholesterol, and triglycerides were measured at each of these examinations. Participants with amputations are identified and the level of amputation was recorded. A death registry was maintained and underlying causes of death were determined by review of clinical records, autopsy reports and death certificates. Terminology and codes of the International Classification of Disease, Ninth Revision (ICD-9), were used to classify causes of death. In the past year, we found that we found that higher 24-hour energy expenditure and resting metabolic rate, measured on different days predict natural mortality in Pima Indians. These findings support a role for increased energy turnover as a risk factor for accelerated aging and early mortality. We also contributed data to a collaborative meta-analysis of 10 cohorts with 266,975 patients selected because of increased risk for chronic kidney disease, defined as a history of hypertension, diabetes, or cardiovascular disease. We found that risk for all-cause mortality was not associated with eGFR between 60105ml/min per 1.73m2, but increased at lower levels. Hazard ratios at eGFRs of 60, 45, and 15ml/min per 1.73m2 were 1.03, 1.38 and 3.11, respectively, compared to an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log risk for all-cause mortality without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 10, 30 and 300 mg/g were 1.08, 1.38, and 2.16, respectively compared to a ratio of five. Albuminuria and eGFR were multiplicatively associated with all-cause mortality, without evidence for interaction. Similar associations were observed for cardiovascular mortality. Thus, lower eGFR and higher albuminuria are risk factors for all-cause and cardiovascular mortality in high-risk populations, independent of each other and of cardiovascular risk factors. In the coming year, we will report on the effect of diabetes on the predictive value of low estimated glomerular filtration rate and elevated albuminuria for all-cause and cardiovascular mortality, independent of other cardiovascular risk factors in a follow-up meta-analysis that includes several other cohorts. Look AHEAD is a multicenter randomized clinical trial of weight loss to prevent cardiovascular disease in type 2 diabetes. We randomized 5,145 adults with type 2 diabetes to a lifestyle intervention or a diabetes support and education intervention for comparison. Eligibility criteria for entry into the study included achieving at least 85% of predicted maximal heart rate and a workload of at least 4 metabolic equivalents and showing no obvious contraindications to exercise in a graded exercise tolerance test. Among the 5783 study volunteers who underwent maximal exercise testing (638 of whom were ultimately excluded from the study due to stress test results that precluded regular exercise), none of whom had symptoms of current cardiovascular disease, 22.5% had exercise-induced abnormalities, including 12.0% with impaired exercise capacity, illustrating a high burden of unrecognized heart disease among older adults with type 2 diabetes. One-year weight losses averaged 8.6% (lifestyle) and 0.7% (diabetes education and support), meeting the goal of a difference of &#8805;5% between groups and establishing the feasibility of testing effects of weight loss. Differences were largely maintained at four years, at which time most measured cardiovascular risk factors were still improved in the lifestyle group compared with the diabetes education and support group. Improvements in risk factors were correlated with the amount of weight lost, but even modest weight loss (5 to 10% of initial weight) was associated with improvements. Participants with severe obesity at entry (body mass index at least 40 kg/m2) had similar percent weight losses as did those with lesser degrees of obesity or overweight.